The G protein-gated potassium current I(K,ACh) is constitutively active in patients with chronic atrial fibrillation

Background— The molecular mechanism of increased background inward rectifier current (IK1) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated IK,ACh contributes to enhanced basal conductance in chronic AF (cAF). Methods and Results— Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective IK,ACh blocker tertiapin was used for inhibition of IK,ACh. Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated IK,ACh was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol/L) reduced IK,ACh in a concentration-dependent manner with greater potency in cAF than in SR (−logIC50: 9.1 versus 8.2; P<0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol/L]-sensitive current at −100 mV: cAF, −6.7±1.2 pA/pF, n=16/5 [myocytes/patients] versus SR, −1.7±0.5 pA/pF, n=24/8), suggesting contribution of constitutively active IK,ACh to basal current. In single-channel recordings, constitutively active IK,ACh was prominent in cAF but not in SR (channel open probability: cAF, 5.4±0.7%, n=19/9 versus SR, 0.1±0.05%, n=16/9; P<0.05). Moreover, IK1 channel open probability was higher in cAF than in SR (13.4±0.4%, n=19/9 versus 11.4±0.7%, n=16/9; P<0.05) without changes in other channel characteristics. Conclusions— Our results demonstrate that larger basal inward rectifier K+ current in cAF consists of increased IK1 activity and constitutively active IK,ACh. Blockade of IK,ACh may represent a new therapeutic target in AF

Incorporation and Degradation of Hydroxyapatite Implants of Different Surface Roughness and Surface Structure in Bone

The interface of dense hydroxyapatite (HA) implants with different surface roughnesses was investigated after implantation into the spongy bone of the distal femur of rabbits by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) following transverse fractures in the interface. Each implant displayed considerable changes in surface morphology caused by leaching (increasing pore diameter), corrosion (particulate disintegration), and active resorption by osteoclasts. Macrophages were involved in cleaning the surface via phagocytosis of loose implant particles. Newly formed surface elevations provided adhesion points for fibers and fibrils. Subsequent mineralization of these areas stabilized the interdigitation of surface elevations and extracellular matrix with adhering fibers and contributed to the tensile strength in the interface. This investigation provides further knowledge about HA implants, which seem to be partially resorbed by osteoclast-like cells

Dynamic Problems of Evolution

Evolution and growth of natural and man-made processes have impressed human beings from the very beginning. What is evolution? Is it the passage from an initial to a higher stage? What does "higher" mean in a world of many objectives? Is "higher" bound to the existence of monotonous indicators like entropy, or is it "gambling" within a predetermined combinatoric multifold of possibilities? Questions of this kind arise from the phenomena in our environment, from the spring-off of new species, but also from processes in our man-made technological world. How is the transition of basic innovation to technology and use of the corresponding products by society, what forecast can be made from increasing CO2, in the atmosphere on the impact on climate, from features of seismologic waves on future events etc. That means there is a strong connection between evolution processes and the emphasis of systems analysis as a help for strategic actions. This paper deals with general considerations about possible growth mechanisms as a base for creating valid growth models. But the main goal is to show how the parameters in growth models can be estimated using on one hand a fuzzy approach together with vector optimization and on the other hand a Bayesian approach. It can be seen that both approaches are useful and applicable and we get informations from one approach which the other one cannot give us. We studied already the growth of cracks in materials, processes well described in [10]. Preliminary results are contained in [13]. Research will be continued to identify the superposition of driving forces and of coupled systems in which oscillations can arise because of time delays between their driving-force pulses

Preliminary verification results of the DWD limited area model LME and evaluation of its storm forecasting skill over the area of Cyprus

A preliminary verification and evaluation is made of the forecast fields of the non-hydrostatic limited area model LME of the German Weather Service (DWD), for a recent three month period. For this purpose, observations from two synoptic stations in Cyprus are utilized. In addition, days with depressions over the area were selected in order to evaluate the model&apos;s forecast skill in storm forecasting

No effect of a parasite on reproduction in stickleback males : a laboratory artefact?

Experiments are often carried out in the laboratory under arti®cial conditions. Although this can control for confounding factors, it may eliminate important factors that under natural conditions mediate the interaction under investigation. Here, we show that different results can be gained in the ®eld and in the laboratory regarding host±parasite interaction. In the ®eld, courting three-spined stickleback males, Gasterosteus aculeatus, were less often infected with plerocercoids of a cestode tapeworm, Schistocephalus solidus, than shoaling males. However, when a random sample of males was allowed to nest and court females in individual aquaria in the laboratory, both uninfected and infected males built nests and courted females. Moreover, while the few infected males that courted females in the ®eld expressed less red nuptial coloration than uninfected courting males, there was no difference in redness between infected and uninfected males in the laboratory. We argue that the different results gained in the ®eld and in the laboratory are due to differences in the cost of reproduction, due to differences in the resource pool of the males. The favourable conditions in the laboratory exclude factors such as predation risk, social interactions, and ¯uctuating environmental conditions that may use up resources in the ®eld and mediate the effect of the parasite

Magnetic Proximity Effect in Perovskite Superconductor/Ferromagnet Multilayers

$\mathrm{YBa_2Cu_3O_7/La_{2/3}Ca_{1/3}MnO_3}$ superconducting/ferromagnetic (SC/FM) multilayers have been studied by neutron reflectometry. Evidence for a characteristic difference between the structural and magnetic depth profiles is obtained from the occurrence of a structurally forbidden Bragg peak in the FM state. The comparison with simulated reflectivity curves allows us to identify two possible magnetization profiles: a sizable magnetic moment within the SC layer antiparallel to the one in the FM layer (inverse proximity effect), or a ``dead'' region in the FM layer with zero net magnetic moment. The former scenario is supported by an anomalous SC-induced enhancement of the off-specular reflection, which testifies to a strong mutual interaction of SC and FM order parameters.Comment: 4 pages, 2 figures, submitted to PR

The D-Grid Integration Project: How to Build a Grid for Different Communities

The Grid world is highly dynamic due to the appearance of new resources, easier access and new Grid applications. Moreover, an increasing number of scientific communities begins to realize that Grids will become an indispensable tool for modern science. However, the requirements of those communities often differ significantly from each other. Therefore, it is a particularly di±cult challenge to establish a national Grid infrastructure that serves as many communities as possible. To address this challenge, the German D-Grid has developed a concept that is based on development of independent Community Grids that are connected with a single integration project. Further, the process will involve several steps to consider dependencies between the various projects and their tasks. Presently, we are still at the beginning of the realization of a German Grid. Therefore in this paper, we first briefly explain this concept in this paper. Then we focus on the integration project and describe its tasks in more detail. This includes some first results and experiences that were achieved within the first year of the project. Finally, some plans for future steps are presented

Addition of Synthetic Feeding Attractant Increases Catches of Rhagoletis batava Hering and Carpomyia schineri Loew. in Fluorescent Yellow Sticky Traps

The addition of the synthetic Rhagoletis feeding attractant (consisting of ammonium carbonate and ammonium acetate, developed previously for Rhagoletis cerasi L.) to both fluorescent yellow or transparent sticky traps significantly increased catches of the fruit flies Rhagoletis batava Hering (pest of sea buckthorn) and Carpomyia schineri Loew. (pest of rose hips). Traps with lures were detecting the occurrence of both species 1–2 weeks before as compared to traps without lure, and quantitative aspects of the flight could be followed in more detail in traps with lure. Thus in detection and monitoring surveys, where sensitivity of the trap is highly important, the use of traps with synthetic lure added is strongly recommended